Flavonoids as Inhibitors of Lens Aldose Reductase

Varma, Shambhu D.; Mikuni, Ikuo; Kinoshita, Jin H.

doi:10.1126/science.1145193

Cited by 172 publications

(67 citation statements)

References 7 publications

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“…Since the mid.-1970's, several studies on the inhibition of aldose reductase by flavonoids have been reported. [14][15][16] However, their structure-activity relationships were not discussed satisfactorily because of the limited number of compounds. In the present study, 94 flavonoids and stilbenes were examined to clarify the further structural requirements of flavonoids for aldose reductase inhibitory activity.…”

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confidence: 99%

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

et al. 2002

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The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC 50 ‫51.0؍‬ m mM), guaijaverin (0.18 m mM), and desmanthin-1 (0.082 m mM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 m mM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3,4-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3,4,5-trihydroxyl moiety).

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confidence: 99%

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

et al. 2002

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“…Scopoletin has also been reported to exhibit moderate ARI activity [25]. Quercetin, a flavonoid that is commonly distributed in the flowers of different plant species, is widely-reported to exhibit strong antioxidant activity and ARI effects [8]. Hence, these compounds were analyzed in this study.…”

Section: Resultsmentioning

confidence: 99%

“…For example, flavonoids, a class of polyphenolic compounds, are known to exhibit a variety of biological activities [7]. Particularly, quercetin, a flavonoid ubiquitously found in many flowers, is known to have strong inhibitory effects against AR [8].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects ofSynurus excelsusandWeigela subsessilison aldose reductase and HPLC-UV analysis of scopolin, scopoletin, and quercetin

Quilantang

Lee

Ryu

et al. 2018

JABC

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The inhibition of aldose reductase (AR) has been shown to prevent the progression of the many complications associated with diabetic hyperglycemia. Several compounds purified from various plant sources have exhibited potent inhibition against AR. In this study, the inhibitory effects of the methanol extracts of the flowers of Synurus excelsus and Weigela subsessilis on AR were determined in vitro. Scopolin and scopoletin are coumarins isolated from the flowers of S. excelsus and W. subsessilis; and quercetin is a known AR inhibitor present in many flowers. To determine and quantify their presence in both plants, HPLC-UV analysis of all three compounds was performed. S. excelsus and W. subsessilis showed potent inhibition against AR having IC 50 values of 0.17 and 0.14 μg/mL , respectively. The concentration of scopolin in S. excelsus and W. subsessilis were 34.71 and 174.14 mg/g extract, respectively. Scopoletin was detected in S. excelsus at 3.41 mg/g extract, whereas quercetin was not detected in both plants. This study shows that S. excelsus and W. subsessilis exhibited promising AR inhibitory effects and are both sources of coumarins.

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“…Also, the type of inhibition by these flavonoids is noncompetitive, a factor preferable in therapeutic use over competitive inhibitors. 27,28) Furthermore, previous studies indicate that common feature of aldose reductase inhibitors is a hydrophobic region attached to an acid group. The flavonoids meet these requirements.…”

Section: Chemicalsmentioning

confidence: 99%

Aldose Reductase Inhibitory Compounds from Glycyrrhiza uralensis

Lee

Kim

Jung

et al. 2010

Biological & Pharmaceutical Bulletin

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We evaluated the inhibitory effects of components from the root of Glycyrrhiza uralensis (G. uralensis) on aldose reductase (AR) and sorbitol formation in rat lenses with high levels of glucose as part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. In order to identify the bioactive components of G. uralensis, 5 prenylated flavonoids (semilicoisoflavone B, 7-O-methylluteone, dehydroglyasperin C, dehydroglyasperin D, and isoangustone A), three flavonoids (liquiritigenin, isoliquiritigenin, and licochalcone A), and two triterpenoids (glycyrrhizin and glycyrrhetinic acid) were isolated; their chemical structures were then elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complication activities of 10 G. uralensis-derived components were investigated via inhibitory assays using rat lens AR (rAR) and human recombinant AR (rhAR). From the 10 isolated compounds, semilicoisoflavone B showed the most potent inhibition, with the IC 50 values of rAR and rhAR at 1.8 and 10.6 m mM, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, semilicoisoflavone B showed noncompetitive inhibition against rhAR. The results clearly indicated that the presence of a g g,g g-dimethylchromene ring is partly responsible for the AR inhibitory activity of isoprenoid-type flavonoids. Further, semilicoisoflavone B inhibited sorbitol formation of rat lens incubated with a high concentration of glucose, indicating that this compound may be effective for preventing osmotic stress in hyperglycemia.

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Flavonoids as Inhibitors of Lens Aldose Reductase

Cited by 172 publications

References 7 publications

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

Inhibitory effects ofSynurus excelsusandWeigela subsessilison aldose reductase and HPLC-UV analysis of scopolin, scopoletin, and quercetin

Aldose Reductase Inhibitory Compounds from Glycyrrhiza uralensis

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